The present invention relates to the methods and apparatus for microscopic screening of cytological samples, and more particularly to an improved computerized method and apparatus for more reliably examining and screening Pap smears and other cytological samples for abnormal cells (atypia).
Typically, the screening of microscopic samples on a slide is accomplished by a cytotechnologist manually moving a microscope stage on which the slide is mounted so as to scan and view, through a microscope, each of the approximately sixty-thousand cells that are contained on the slide. In a typical laboratory environment the cytotechnologist is expected to review over ten such slides per hour. Thorough examination is required since a single abnormal cell (atypium) in the approximately sixty-thousand cells, may be present. Importantly, the single atypium may be sufficient to achieve early detection of, e.g., an incipient carcinoma or symptom of cervical cancer. Unfortunately, the false negative rate in commercial screenings, such as Pap smear screenings, is typically 10% or worse, even though a rate of 1% to 2% is medically achievable.
After the cytotechnologist has scanned the slide, each suspected positive, that is those slides containing possible atypia, and a portion of those slides that the cytotechnologists have determined contain no abnormal cells, are rescreened by a pathologist for a full diagnosis. To facilitate atypia relocation, the cytotechnologist physically marks the slides with a paint dot placed near the abnormal cell or cells. The pathologist can then restrict his or her rescreening to searching in the vicinity of the paint dots for the suspected abnormal cell or cells found by the cytotechnologist. Unfortunately, because of inexactness in the location of such paint dots and the size of the paint dots relative to the suspected abnormal cell or cells, considerable time is still required for the pathologist to relocate the suspected abnormal cells and to fully diagnose each rescreened slide.
Thus, in practice, much of the time spent by the pathologist, and by the cytotechnologist, is unfortunately spent performing non-diagnostic functions such as relocating suspected abnormal cells. Because such non-diagnostic functions distract from more important diagnostic functions, they contribute to the above-mentioned high false negative rate. Furthermore, the additional time that is spent screening each slide significantly increases the costs associated with routine medical screenings, such as Pap smears.
One prior apparatus and method which addresses the foregoing is described in U.S. Pat. No. 3,851,972 ('972 patent), issued Dec. 3, 1974. In the method of the '972 patent, individual cells are relocated through computer memorization of coordinate signals representative of a specific cell's location on the slide. Cell location is memorized as stage x and y coordinates, (as taken from step counters) referenced to the instrument's "Home" position, that is the position of the stage when the slide is loaded onto the stage. When the slide is reloaded onto the microscope stage, a mechanical assembly returns the slide to its original position based upon the memorized coordinates. Unfortunately, such operation requires highly repeatable and precise repositioning relative to the stage's home position, and relative to the instrument's optical axis. In practice these requirements result in excessively demanding tolerances on mechanical components and electrical drive circuitry, with correspondingly high hardware cost.
In other instruments unrelated to automated microscope systems, such as in numerical-controlled machine tools, and in some research automated microscope systems employed in scientific research, closed-loop positioning systems (positioning servos) incorporating linear encoders or similar sensors are used to provide precise positioning (sub-micron accuracy) of a controlled element. Such research automated microscope systems utilize a specialized precision stage in order to achieve such precise positioning. While the degree of precision permitted by such systems may satisfy the requirements for some microscopy applications, the hardware cost is much too high to permit their use in commercial automated microscope systems.
Another problem in screening microscopic samples is that the microscope used by the cytotechnologist may be a different microscope than that used by the pathologist to later relocate the possible atypia. This is common since a pathologist will usually work with and rescreen the slides of a number of cytotechnologists. Unfortunately, instruments and systems such as those described above, which record the location of atypia, or other features, using stage-dependent x and y coordinates relative to the home position of particular microscope stages, are not useful unless the pathologist is using a microscope that is identical to the microscope used by the cytotechnologist. This is because the location of the possible atypia are recorded relative to the home position on a particular stage of a particular microscope. Both the locations of the home position, and the measured location of the atypia relative to the home position, are highly dependent on the mechanical structure and precision of the microscope stage. Furthermore, the automated equipment or automated positioning system used to reposition the microscope to the exact location of the possible atypia must be extremely precise, and must perform identically in each of the microscopes unless positioning servos are utilized so as to compensate for differences in movement patterns of, e.g., the stages of the two microscopes. In either case, such equipment is very expensive.
Even such prohibitively expensive microscope systems do not offer a complete solution to the problems created by the use of different microscopes during screening and rescreening. As such microscopes are used, and thus, as the stage and positioning equipment wears, such systems become out of tolerance. As a result, accurate repositioning of a microscope, based on position information obtained from another microscope, becomes increasingly difficult, and eventually impossible.
Thus, a further problem with the system of the '972 patent arises because the '972 system uses coordinates that are measured relative to a particular stage. Specifically, both (i) the discrete motor steps along the x and y axes that are counted and used to identify locations on the slide and (ii) the angular relationship between the x and y axes, are dependent on the particular automated positioning equipment used to position the stage of the '972 system. In other words, the '972 system uses a microscope-dependent coordinate system to identify the location of the features on the slide. Thus, microscopes other than the microscope used to locate the features (or an identical microscope) are not able to accurately relocate the features. Therefore, the '972 system is not suitable for use in a multiple microscope environment.
The present invention advantageously addresses and overcomes the forgoing problems and shortcomings of prior microscope systems.